Episode #91 | 3D Printed Pharmaceuticals (Virtual Event Recording)

What if your medication could be made just for you? No more pill overload and no more awkward dosing workarounds. Just the exact treatment you need when you need it. That is the promise of 3D printed pharmaceuticals.

Drug manufacturing has relied on a one-size-fits-all model for decades. Nearly half of all medications lack proper formulations for children and seniors are often left struggling to manage boxes of pills each day. It is time for a smarter, more personal approach.

In this episode, you will hear how innovators around the world are reimagining what medicine can be. Dr. Alvaro Goyanes, CEO and Co-Founder of FABRX, explains how his team launched the world’s first clinical application of 3D printed drugs in 2018, paving the way for personalized dosing. From Singapore, Dr. Seng Han Lim, Co-Founder and COO of Craft Health, describes how their heat-free printing technology protects fragile biologics that traditional methods destroy. And in Finland, Dr. Niklas Sandler, Founder and CTO of CurifyLabs, shows how they are bringing 3D printing directly into pharmacies with compact printers and cartridge systems, giving pharmacists the ability to produce safe, customized medicines on demand. To ensure these advances are reliable and widely adopted, Dr. Thomas Forbes of the NIST shares how the institute is building essential measurement standards for printed pharmaceuticals.

From shrinking the pill burden for tuberculosis patients to tailoring cancer treatments for individuals, the breakthroughs are already here. The possibilities are just as striking looking ahead. Just think of on-demand medicines in disaster zones, or astronauts printing personalized therapies on long space missions.

This conversation offers a front-row seat to the future of medicine, whether you are a healthcare professional, technologist, or patient advocate. Tune in as we explore how 3D printing is not only changing the way drugs are made, but also redefining what medicine can mean.

Watch on demand: https://3dheals.com/courses/3d-printed-pharmaceuticals/

Event highlight shownotes

Youtube highlights

Chapters

• 0:00 Episode Introduction
• 3:03 FABRX: Pioneering 3D Printed Pharmaceuticals
• 28:25 Craft Health: 3D Printing for Personalized Medicine
• 53:06 Curify Labs: Automating Pharmacy Compounding
• 1:14:22 NIST: Measurement Science for Pharmaceutical Production
• 1:38:00 Panel Discussion: Industry Challenges

Transcript

Speaker 1: 0:05

Hello, hello, good morning. It's me again, jenny Chen, founder CEO of 3D Heals. We've been doing this webinar series for quite a few years now. 3d Heals as a company has three mission. One is to educate the public about what 3D printing and 3D technology can do for healthcare, and today is one example of that. And number two mission is to create an environment for networking.

Speaker 1: 0:32

We haven't hosted a lot of in-person events since the pandemic, but we hope to restart and we have hosted a few, so stay tuned in our newsletters if you want to join some of that. But virtual events can be effective also. One is you can learn, probably focus better and you can see the slides better without squinking your eyes. Number two is you can put your social media information in the chat box, or just chat, whatever the chat box is for socializing, so you can tell people who you are, what you're looking for. However, the only thing you shouldn't put in your chat box is questions, because I cannot keep track of your question if you don't put them in a QA box. So make sure you put them in a QA box. Okay, so that our number two mission. Number three is we have a program called pitch 3d. We focus on helping early stage startup in this space. So 3d technology in healthcare, with fundraising and there's no fee associated with it whatsoever, as long as you qualify, and we introduce our startups to a group of institutional investors on a regular basis, and so reach out to me if you're interested.

Speaker 1: 1:51

All right, let's talk about the topic today. Today's topic. We have been presenting this topic for a number of years. I'm investing in one of the startups here, craft Health, and I am very passionate about this space because, as a doctor, I know how dangerous polypills can be for elderlies and just in general, like why would you want to take a dozen of large pills when you can combine them into one? So the idea sounds really attractive to create personalized pill that's more easily ingested and more effective.

Speaker 1: 2:27

But where we are? Because the concept sounds amazing, but implementing, commercializing it, is another story. So we have a group of experts, a really phenomenal panel of pioneers in the field and people who really will make a dent in the future of 3D printed pharmaceuticals and nutraceuticals today. So I'm really happy we have this great group of people and I had a quick glance of our audience list and hopefully quite a few people that I know are going to join the live audience. I know they're also very knowledgeable in the space, so it's going to be an amazing conversation. Without further ado, I'd like to introduce our first speaker, dr Averil Goianes. He is the CEO and co-founder of FabRx, which is considered one of the first companies in the space of 3D printed drugs. Averil, you are on. Maybe you can unmute yourself and start presenting perfect, great.

Speaker 1: 3:28

Thank you and everyone else can be off screen and mute themselves.

Speaker 2: 3:31

Thank you so much thank you for the introduction and thank you for the opportunity to present here. I'm going to share my screen, whole screen, so hopefully you are going to see my presentation full screen. Now, correct, yeah? So yeah, the company Fabrics. I'm the CEO and co-founder of Fabrics. Fabrics is a spin-out company from UCL University College London. We are based in London, but we have a subsidiary company in Spain, in Europe, that is Fabrics AI, more focused on the use of artificial intelligence for the development of medicines, the dose prediction, everything related to 3D printing. And we have also fabrics in the US for our customers in the US.

Speaker 2: 4:26

I'm going to talk about 3D printing in hospitals and pharmacies and how fabrics. What is our vision in fabrics? So, the benefits of pharmaceutical 3D printing when we are talking about pharmaceutical 3D printing, we are talking about a layer by layer process, additive manufacturing, and in this process, thanks to this process, we can print formulations like oral dosage forms. We can print implantable devices that we can insert in the body and release drug during months or weeks, and I'm going to focus mainly in oral formulations. What is the advantages of using 3D printing for oral formulations? We can automate compounding, make medicines more personalized in terms of doses, flavors, colors, shapes. We can make medicines safer because we have different quality control methods inside the printers we are printing in hospitals and pharm control methods inside the printers we are printing in hospitals and pharmacies, closer to the patient. So we are more environmentally friendly, reducing carbon footprint, reducing the stock of medicines with different doses and, thanks to 3D printing, we can have faster and cheaper clinical trials for the development of new medicines faster and cheaper clinical trials for the development of new medicines.

Speaker 2: 5:48

So how we started? We started in 2014. I was a researcher. I have two hats my academic hat with the University College London, I'm an honorary lecturer there and I'm also a professor in the University of Santiago de Compostela in Spain. So I do a lot of research and I also have my business hat, that is with fabrics.

Speaker 2: 6:08

So in 2014, when we started doing research about 3D printing, we were saying we are going to print medicines in hospitals and pharmacies. Everybody was laughing because they thought it would be impossible. So in 2018, we did the first clinical study where we print medicines with a 3D printer in a hospital and we print chewable tablets for patients pediatric patients with a rare metabolic disease. This was a groundbreaking study because we proved that 3D printing could be implemented in hospital. Thanks to this study, we got a grant to develop the first pharmaceutical 3D printer, launching to the market in 2020. It's the MediMaker. And since then we have done more clinical studies. We printed medicines combining two different drugs, so drugs combinations with high dose, also for rare metabolic diseases. Since then, we were the first using a 3D printer in a pharmacy, in a normal pharmacy, community pharmacy, and we published the first article with a 3D printer implementation in a community pharmacy. Since then, we have been doing multiple clinical collaborations, partnerships with the best hospitals in the world, pharmaceutical companies. We are involved in more than 30 clinical trials all around the world.

Speaker 2: 7:37

And also we were contacted by NASA because in our vision and one of the articles we published, we publish more than 110 articles. One of the articles we publish the title is To Infinity and Beyond Strategies to Make Medicines in Outer Space. We grabbed attention of NASA and we were visiting Cape Canaveral Kennedy Space Center. The chief medical officer from NASA, jd Polk, gave us a tour there. How can we implement 3D printing in space, in different planets? Because 3D printing is definitely the future. So when we are talking about 3D printing, we are talking about layer-by. We are talking about layer by layer process. If it's not layer by layer process, it's not 3D printing, it's something else. But with our 3D printers sometimes we find partners or customers that tell us well, 3d printer sometimes takes time, we want something faster. So with our 3D printers we are able to print inside blisters, so do blister filling, and to print inside capsules. It's the same 3D printer using more or less similar materials but under different conditions. So blister filling and capsule filling is faster because we are not worried about the shape. But obviously it's not 3D printing, although we use a 3D printer. In one of the studies in a pharmacy it was very interesting because we proved that with a 3D printing we can reduce manual labor, reduce production cost per medicine and we were able to produce thousands of tablets per day.

Speaker 2: 9:26

In the video you can see how the process is. You select a pharma ink, you scan it, you put it in the printer, you select the doses that you want to print. It prints directly into the blisters. The balance under the blister is recording the weight of each individual formulation. Then you close the blister and you give it to the patient. So this is also safer for the pharmacist because there is no high exposure to the medicines for the pharmacist.

Speaker 2: 9:57

How is the process? Well, if we cannot buy a pharma ink, we need to wait excipients and drugs, following a SOP, a protocol that is in the software. We put that in a syringe. We melt all the materials in the syringe, then we select the syringe, we put it inside the printer, we select what we are going to do 3D printing, capsule filling, blister filling. The doses that we are going to print, we need to enter our code and then we print. We print and record the doses at the same time. Here is with a capsule filling minoxidil formulations. That is a study that we did in a pharmacy and we can see how the weights are recorded and how we can get a report with the weight of all the formulations that can be stored. So this is conventional clinical practice. It's not science fiction. It's something that can be integrated in a pharmacy right now and we have printers in several pharmacies in different countries Europe, us.

Speaker 2: 10:56

So how we work we offer the pharmacists the opportunity to select many different materials from many different providers. We don't ask the pharmacist to buy materials from us. Why? Because we are in Spain or in London or we are in one state in the US, but maybe the best material arrives faster from a company like Specialized Rx or PCCA or Medisca or Meta Pharmaceuticals. So you select the materials you want to use. You put them in a container from GACO or a waiter container. You mix everything, put it in a syringe, put it inside the printer and print.

Speaker 2: 11:36

We have different quality control methods. The most important one is the balance, because you know the weight of each individual tablet. We have a pressure sensor that identifies when we are extruding if there is any problem. So the pressure diagram should be always the same. If it's not the same, we know there is a problem with the formulation. And additionally, we can add NIR, near infrared to know the concentration of drug inside the formulation. Nir is more research-oriented and it doesn't work with all the drugs, but with many drugs NIR can be used.

Speaker 2: 12:12

So the software is key because you need to have all the libraries, the protocol libraries. There you can share protocols with other pharmacies. It identifies the QR codes and barcodes from the syringes, the blisters, the base, and has automatic audit record so you can keep everything in the software. We have many partnerships with compounding suppliers so you can buy materials from them. We have collaborations with pharmacies, obviously because they implement this to treat patients. We have collaborations with universities, research institutions, pharmaceutical companies like Pfizer. We published recently an article where, with the team at Pfizer, we were using 3D printing for clinical studies, first in human clinical studies. We have more collaborations with other pharma companies that we cannot disclose. Some of them are for oral formulations, some of them are for implantable formulations. That I'm not talking that much here because I think the focus is more oral Partnerships. Collaborations with the Center for Disease Control, us Pharmacopeia. We are taking part in discussions with the FDA European Agency Quality Innovation Group For us regulation is key and we have partnerships with many hospitals around the world, so I cannot include all of them here.

Speaker 2: 13:43

I would like to highlight Gustav Russi. It's the biggest hospital for cancer research in Europe and I think it's the leading hospital in the implementation of 3D printing. They have two of our Medimaker 2 that has multiple printheads so they can do drug combination, anti-cancer drug, pediatric medicine for cancer treatments, anti-cancer drug, pediatric medicine for cancer treatments, taste masking. So what they do is at the forefront of research and implementation in the world right now. We have partnerships all around the world. We have printers in India, china, japan, saudi Arabia, europe, brazil, many different countries, even Africa as well. So what we want is to collaborate with everyone to implement and move our dream that started in a small lab in UCL all over the world and make 3D printing a reality. That we think is a reality right now, but we are very happy to work and have partnerships with everyone.

Speaker 2: 14:47

So, as a company, what we offer is the printer, the Medimaker, state-of-the-art technology with balance pressure sensor, nir. We have the software to control the printer. We don't want the pharmacist to know anything about 3D modeling, 3d design, just select the dose and print. And we developed PharmaInk. Pharmaink is a mixture of drug and excipients Excipients whatever excipients you want to use, conventional pharmaceutical excipients and any drug. We were printing many different types of drugs.

Speaker 2: 15:20

So when I was invited to this conference, I wanted a list of things that we need to consider when we are talking about 3D printing. One of them is a type of medicines that we want to design for the patients If we are talking about chewable tablets, oral dispersible tablets, films, capsules, strokes, suppositories. So is the printer able to do all of that? Our technology is Acceptability of the medicines. We need to ask patients what they want. Obviously we need to make them attractive to the patients not too attractive to children, but attractive to the patients and for that we need to do clinical studies and ask patients what they want, what they prefer, and this is what we do.

Speaker 2: 16:07

Selection of drugs which drugs are the most beneficial for the technology? We were printing many different types of drugs. I think we have a library with more than 150 drugs. We printed antibodies, small peptides, crazy drugs. Many of them we cannot disclose because they are in collaboration with pharma companies. But it's critical to select the right drug.

Speaker 2: 16:34

Are we able to print the drug in the range of doses? That is the correct one, because maybe we can print the drug at 5 milligrams or 10 milligrams. That's very easy, but many times the difficult part is to print in the whole range. That's why 3D printing is very important. We were able to print medicines with drugs at 1.2 grams, so 1200 milligrams, and it's very high. For that you need 3D printing, something that is layer by layer With filling, although it's faster, you cannot reach sometimes this high drug loading, maybe 500 milligrams but are you able, with your technology, to reach the therapeutic drug level? This is critical because maybe you print with one drug but you don't reach the therapeutic level and you need the whole range, maybe from five milligrams to 500 milligrams.

Speaker 2: 17:29

Is the technology able to do that? Yeah, published data formulations are openly disclosed to have clear understanding of what the excipients you are using the pharmaceutical excipients that you can get from an approved provider in your country. And we published all the data, or most of the data, only data that is confidential we cannot publish. We evaluated all the 3D printing technologies FDM, semi-solid extrusion, sls, sla all of them. Fdm, semisolid extrusion, sls, sla all of them and we selected the ones that we think are the best for this. That are material extrusion, semisolid extrusion, fdm that uses filament for implantables, and direct powder extrusion that use a powder. And then regulatory approval. At the beginning, we started with a food printer. It was a disaster.

Speaker 2: 18:27

You need a pharma printer that works and is especially designed to print medicines. It's very important. The certificate of the syringes because they are in contact with the drug are syringes that are certified. Our syringes are easy to use because if they are not easy to use, users are not going to use the technology and easy to clean, so validated cleaning protocols are very important.

Speaker 2: 18:56

It's important to consider what the formulations are going to be, if they are going to need refrigeration or not. If you need to keep them in a fridge, maybe it's not so attractive for patients. So ideally, you want your formulations to be water-free. The one that you see in the video looks like liquid, but it's not a liquid. It's based on polyethylene glycol that melts at 60 degrees but then solidifies immediately, so it's water-free, and the stability of these formulations is very long so more than six months and it's important if you are going to use this technology for clinical studies or for a standard clinical practice, you need to have this versatility. So this is my presentation. We have a lot of webinars in our webpage, so if you go to fabricscouk webinars, we have more information and you can send me emails and I'm happy to discuss potential collaborations. That's all, thank you.

Speaker 1: 19:55

Thank you. I cannot believe you guys published what 100, more than 100 papers.

Speaker 3: 20:00

Yes.

Speaker 2: 20:01

That's crazy. Yeah, we are very productive.

Speaker 1: 20:06

Okay, well, that's a very comprehensive, excellent presentation. I learned so much. Every time I see your presentation, I thought I already knew everything, but no, you always have something new. Can you tell us some of the limitations that you're experiencing right now with your current system and what are you working on in terms of challenges? I think you're muted somehow, I don't know why, sorry.

Speaker 2: 20:29

I don't think there are technical limitations. I think there are limitations. The main limitation of implementing 3D printing is awareness. Many people see this technology like a far technology, futuristic technology, so forums like this are important to show people that this can be implemented. We are in many hospitals, many pharmacies and this is there. So one of the limitations is probably lack of awareness and, obviously, people using printers. They never study 3d printing in their pharmacy degrees or things like that, so we need to create a specific programs for that. I'm also the the chair of the pharmaceutical 3d printing initiative that this initiative that wants to bring together people from academia, industry, regulation to actually implement this technology. So we are not just a company trying to make money. We actually want to change the world and implement this technology. So that's why we need to come together to push this.

Speaker 1: 21:38

Yeah, I love that vision. Yeah, same here. Now another question is of all the cases that you can actually share with us because I know some are preparatory, but the ones that you can share, which one is the most impactful and promising that you have seen so far?

Speaker 2: 21:52

so one. I mean we have many. Uh, the ones that gustav russi, they are doing are for me the best ones, because even for me, when they tell, me that's the cancer institute right exactly gustav russi is the hospital in france.

Speaker 2: 22:04

They tell me that's the Cancer Institute, right, yeah, exactly, gustave Roussi is the hospital in France. They tell me oh, we are doing this, for example, printing one drug that is for cancer, to treat breast cancer, in pensions with one of the two drugs to avoid the side effects of this medication altogether. So they are printing that and for me that's crazy because they are doing drug are printing that, and for me that's crazy because they are doing drug combinations straight away. And I was telling them well, go step by step, one drug at a time, slow, no, they were like full on developing formulations. Then we have a partnership with a company doing implants for anti-cancer drugs as well, so removing tumors and putting plants with anti-cancer drug so it's not just oral medication anymore no, no, no.

Speaker 2: 22:50

We we have a some crazy projects crazy in terms of crazy projects.

Speaker 1: 22:56

Yeah, I thought I heard it wrong. I was like no, it's actually. He said crazy, okay, yeah, yeah it's a.

Speaker 2: 23:03

I mean crazy, because it's like shocking innovative. When I translate from Spanish, the word for me is crazy, but maybe in English it's not the right word, but it's really exciting projects, yeah.

Speaker 1: 23:18

Okay, great, thank you so much. Okay, we have a couple of questions from the audience. One is from Shubhansi much okay. We have a couple questions from the audience. Um, one is, uh, from a shoe band scene. I'm preparing 3d printed tablets. How we select free ability and hardness parameters? Okay, so, mechanical properties. Parameters for print.

Speaker 2: 23:37

Yeah, so friability and hardness, or breaking force, are some parameters that, according to the pharmacopoeia, are probably more focused on traditional tablets. For example, if you are printing directly into a blister, you don't need to do friability and hardness. Why? Because normally you are going to remove it from the blister and take it. So these parameters are useful for when you are in an industry and the tablets are going to be in big drums and then you need to pack them.

Speaker 1: 24:09

So yeah, so there you go. That's the 3D printing education Exactly.

Speaker 2: 24:14

There are no specific requirements for these tablets. So you can do the standard method and say like well, the relevance of these results is what it is.

Speaker 2: 24:25

Okay, another question from Luciano Vragio uh, sterile, sterile, sterility, um yeah, how do you keep them sterilized? Basically, yeah. So, uh, for example, for implantable devices, uh, what we have is we have the printers in fume hoods or in hoods that are inside GMP clean rooms. So we sterilize the printer from outside, but most of the time for implantable device, you sterilize the product after production. This is the standard practice as well For oral formulations. You are not aiming for sterile formulations, they are just oral formulations. You can have them in GMP areas, especially for clinical studies, but sterility is not a requirement. But for medical devices drug-loaded medical devices, yes, but normally the process is that you do a sterilization after you print.

Speaker 1: 25:27

Okay, and then you mentioned sterilization of the syringes. What's the process for that?

Speaker 2: 25:35

What is important is that the syringes that you use are approved to be in contact with drugs at these temperatures, that there are no products that go into the formulation and that the materials don't interact with the syringes, because the syringes are in touch with the drug and you are going to swallow these formulations.

Speaker 1: 25:55

That's what is important okay, let me see I have another question. Uh, we have a lot more questions. You may have to type in the answer because, um, I want to keep us in the same pace. So let's just pick one more. Let's see Wow, it just keeps coming here. Let's see Okay, so from Jack, I run a pharmacy business For scale-up how much material, both API and and excipients, can you support every month in kilograms? It sounds like something else, but no, it's not. But that's a good question.

Speaker 2: 26:32

Okay, this is a very practical question so yeah, it depends on the use you give to the printer. In some pharmacies they use the printer one or two days like full and then they don't use it the rest of the week. So during these two days they prepare 8,000 or 10,000 formulations per day. I don't know what is the bulk material. I know they have big drums of materials like three kilograms and things like that, but they use it for two, three days. Other pharmacies they print every day some formulations. It depends on the state, I mean the country. So in the US it's possible to get some batches. In other countries in Europe you need to make the batch just for the patient. It depends on the regulation.

Speaker 1: 27:22

Yeah, you do not provide the materials, you just provide the system to make the medication.

Speaker 2: 27:27

We provide the system, the know-how, the materials. We recommend them to buy the materials from local providers. We recommend some materials, we give the protocols, but we don't sell the materials. If they don't find the materials, for whatever reason, we can't provide the materials, but our business is not selling materials, great. We are a company doing AI hardware software, not selling materials.

Speaker 1: 27:55

Yes, you're the first company I heard in the space actually use machine learning, even before the hype of AI. So good, first starter. So we have quite a few questions, but I don't think I'm gonna address all of them just because of time.

Speaker 1: 28:09

You can feel free to type in the answer. And also, guys, if you want your question to be a priority, just type them in while the speaker is still talking, so that I can get them in. All right, thank you so much, professor. I'm gonna introduce our next speaker, okay, okay, our next speaker is Dr Sing Han Lin, another doctor. We have all the doctors here today. He is the CTO and co-founder of Craft Health, a company in Singapore also working on 3D printed drugs all right, hello everyone.

Speaker 3: 28:55

Thank you to jenny and, of course, 3d hues for the kind invitation and, of course, for this uh, excellent platform itself that allows us to really have this wonderful discussion with some of the world's leading 3d printing pharmaceutical company. So, without further ado, let me actually just share my screen. I think everyone is able to see. So, really, the title of my discussion today is really about 3D printed pharmaceuticals and how is it an avenue towards personalized medicine. At the same time, I'll also discuss some of the key barriers that we believe is actually key barriers to mass adoption of 3D printing in terms of personalized medicine, and how we believe that our craft health platform technology itself is an enabler to the adoption of 3D printing. Alright, so a little bit more introduction to myself. I'm a pharmacist by training, so I practiced for a few years in a local general hospital that's a Singapore general hospital. Subsequently, I went on to do my post-grad studies whereas that is when I actually picked up some of the skill set. My thesis was basically on 3D printing for personalized joint delivery and testing systems. So fast forward, about 10 years later now I am the co-founder and the CTO COO of actually CraftHealth, where we are based in Singapore. Other relevant experiences really is due to the work that I do. I am a technical member of the Singapore Standards Council that looks at the review of some of the additive manufacturing-related standards.

Speaker 3: 30:17

Now, really, the mass-produced pharmaceuticals they have been around for many, many years and everyone is so used to actually consuming them. However, definitely I think there are some issues with the clinical use of these mass-produced pharmaceuticals, especially for specialized or special populations such as the elderly or the pediatrics. The need for customized dosing, such as for pediatrics with dosing by weight, is sometimes not available in a lot of these mass-produced pharmaceuticals, and every one of us will have consumed such medications before, and sometimes the doctor will ask you to break the tablet into half, break the tablet into quarter, and all these are really not that accurate. Polypharmacy and complex medication schedule would often also result in maybe non-compliance and undesirable efficacy itself. So that's something that is also a clinical concern for mass-produced pharmaceuticals.

Speaker 3: 31:06

Unavailability of finished products meaning, for example, like Singapore, with such a small market size as compared to the US, there are a lot of products, a lot of finished products, meaning, for example, like Singapore, with such a small market size as compared to the US, there are a lot of products, a lot of finished products that do not reach us, that do not register in such markets like Singapore. So therefore, what is the clinical use of such finished products, where they are not available, actually available in a small market like Singapore? And definitely some of the dosage forms that we have now are also not that suitable for swallowing, and I think this is also some concern that we should address as well. So, with all these clinical use and clinical concerns, I think there's really opportunities for innovation or even personalization of the different dosage forms. Number one would be really on-demand tablets with personalized dosing. There's also opportunity for innovation in terms of personalized polypill with different release profiles to help reduce the pill burden, on-demand compounding for actually non-registered finished products and definitely also the innovative and patient-centric dosage forms that help patients with swallowing difficulties. And really could 3D printing be a solution for all these different opportunities and innovation? So the key advantages for 3D printing in pharmaceutical is really the ability to actually have complex geometry itself. 3d printing can easily do things like a core and a shell that actually encapsulate around to do either taste, mark, scan or control release profiles. Other than complex geometry, 3d printing also allows rapid prototyping and ease of usage, so definitely something that is really useful for R&D or even for university for research kind of work. For 3D printing in pharmaceutical Personalization could also be one of the key advantages of 3D printing. That's probably also related to the cost efficiency for small quantities production using 3D printing. That's probably also related to the cost efficiency for small quantities production using 3D printing itself.

Speaker 3: 32:57

Some of you may have seen this before. If you are looking at traditional manufacturing or traditional tablet press itself, the more units of the same kind of tablets that you produce, really the cost per unit itself drops drastically from here all the way down. Then it's not so much of the case for 3D printing because really 3D printing there's no mold involved. So conversely, there's no high upfront capital cost itself in terms of investing the most and so on. However, as you scale up to a large number, you realize that 3D printing, the cost per unit itself probably remains the same. Now, if you're willing to cross-intersect this to a graph itself, you realize that there is actually a very, very good area of opportunity, which is the high-value niche personalized healthcare itself where 3D printing could really shine. Now this sounds like a no-brainer for actually 3D printing itself to be involved in such personalized healthcare or personalized medication itself.

Speaker 3: 33:54

However, the reality is that we are not seeing 3D printing being picked up as rapidly or as prevalently as we would want around the world itself. And then we wonder to ourselves what are some of the key barriers that actually is preventing all this mass adoption of 3D printing for pharmaceutical dosage form? We believe that there are three main class of key modifier barriers to mass adoption of 3D printing for personalized medicine. Number one is based on the technical side itself. There's really a lot of different 3D printing technology outside from the FDN, the SLS, SLA, sse, so on and so forth, but there's really no one size that fits all the different APIs, all the different active ingredients, all the different dosage forms that one can think of. There is also, of course, when you want to pass on this technology to the end user, such as the compounding pharmacies, the pharmacies in the hospital, for example. There is often a huge learning curve in terms of the use of 3D printing platform. The second category of key modifier barriers for us, everything is the logistical issues. While most of the excipients that's being used in 3D printing are largely similar, but really, if you want all of the end users, such as the compounding pharmacies, to actually procure and to maintain all the different quality starting materials. Those are going to be quite a challenge if they were to maintain that on top of what they are already having. And, of course, finally, the regulatory some of the could be one of the modifiable barriers as well, because currently there's really no clear guidance to setting up a 3D printing pharmaceutical facility or even adopting the 3D printer for printing of pharmaceuticals itself. Now that is where we believe the CraftHealth printing platform itself could actually help to mitigate some of these barriers. So let me allow me some time to actually introduce what we have over here at CraftHealth. What we're trying to do is really to embed platform solutions in industries towards their efforts for automated mass customization.

Speaker 3: 35:57

We were founded in 2019, so as of now, we are already a six-year-old company. We are a spin-off from National University of Singapore. We are currently located at this area. This is the Jurong Town Council or JTC Launchpad area in Singapore West side of Singapore where it's really a congregation of the different startups, accelerators and venture capital itself, with the aim of actually promoting and increasing the visibility of technologies in Singapore. Now, over at our facility, we have the sales office, general office, r&d lab and a mini production area itself. As of now we are primarily venture-backed.

Speaker 3: 36:35

A typical 3D printing process of pharmaceuticals. So if you go to Google, basically the typical 3D printing process that's involved will only start from designing, slicing, printing and post-processing. But that is really because a lot of 3D printing processes they are using standardized materials such as maybe ABS or PLA itself. For any 3D printing of pharmaceutical, the entire process really starts from developing the own formulations itself. So often it is tedious formulation development. So those of us who do R&D for pharmaceutical formulation, you will know that it can often take weeks to months to get the desirable dissolution profile, desirable characteristics and so on. But once you're done with the R&D, you'll do material preparation. And also for 3D printing, the volume that's being printed correlates strongly to the dose that is eventually found in each of the finished products. So you need to determine the volume that they printed, which then finally design, slicing, printing, post-processing and so on. We think that all these different steps are really cumbersome and time-consuming. So over at Craft Health we try to reduce that by providing standardized premixers, where we call them craft blends, to actually provide an easy formulation development process, after which we have, of course, standardized SOPs operating process for material preparation. We know that a lot of our customers, a lot of our pharmacies, do not really want to deal with all the designing work, slicing work, so really, we also provide the standardized templates for them to select and print so that can really reduce the overall learning curve and reduce the time spent on developing and optimizing the 3D printing process for any of the new finished products that they may have in mind.

Speaker 3: 38:18

So this is where I introduce CraftEnable. This is basically a platform for software subscription itself. This is for standard formulas for any new APIs using our CraftBlends premix itself. Really, a customer, a pharmacist, for example, if they have an active ingredient in mind, they can just change some of the parameters into our premix calculator. They'll be provided with the recommended composition, the recommended weight itself for them to prepare the different premixers, prepare the active ingredients, mix them together in a standardized method and then we'll get the printing material out. We also provide them with recommended 3D printing G-codes which, in this case, these are the printing instructions for the pharmacist to actually load them onto the printer. So in this case, for example, there will be a standardized template for 700 mg total with immediate release, tethered in this case, of course, our calculator. If the pharmacist would enter something that is out of the range, that doesn't work for sure, there will always be prompts to tell them that this is something that is not going to work. We will want them to either do some changes so that the formulation will work with our Kraft-Benz pre-mix.

Speaker 3: 39:32

So over at Kraft-Benz we have a full integration of the formulations, software and also the hardware itself. Our formulation, craftlens, already consists of XCPNs on the US FDA grass list, all found in the US FDA inactive ingredient database itself. By changing the XCPNs we are able to control the different release profiles, which, namely, that we have is for immediate release, sustained release, delayed release and, lastly, the one that we have is actually for GAMI formulations. Of course, our software-wise CraftControl is a suite of software that is optimized for our printer and it also provides an auditory function for GMP compliance. Finally, that is for our printer, and we also provide an auditory function for GMP compliance. Finally, that is for our printer itself, called CraftMate.

Speaker 3: 40:15

I think a unique selling point is that again, it is semi-solid extrusion. There is no heat, no UV required for the printer itself. This allows us to incorporate a wide variety of active ingredients, for example some of the really up-and-coming peptides, biologics. They are heat sensitive. This can be actually produced through the use of our printer. Basically, this is just a simulation of the dissolution of the tablets that are printed in a simulated gastric fluid itself. We can do different release protocols, all packed into a single tablet, for example a two-layer tablet, three-layer tablet or even a four-layer tablet itself, which, in this case, for the four layers, these are all immediately released within a 20 minutes range itself. One thing to note our craft blends. These are standardized premixers and we could go as high as 80% of the dry loading for our active ingredient itself.

Speaker 3: 41:14

Software-wise, our craft control suite of software. Of course there's always the back-end side where you do designing and slicing one, but that's not something that our pharmacists will actually want to do on a daily basis. So really, most of the time they're just going to deal with a wireless interface, in this case over here, where they can print, they can monitor and provide an auditory function for that. So some of the key features on this wireless interface will be things like you can have your file management over here. You can have a real-time monitoring and center, also in terms of a GMP compliance. You can have access control to see who are the admin, who are the operators that can log in through the system to control the printer itself. At the end of each print there will always be a print job report that looks at what was the printer that is being used, what are some of the printhead IDs, some of the materials that is being used start time, end time, so on and so forth.

Speaker 3: 42:05

Now this is our printer itself CraftMate 3D printer series. What you see here is actually the CraftMate production, where there are two printheads that can print two different materials concurrently onto two separate tablets itself. So this really helps us to improve the production speed. We also have another smaller model, that is the Craftmade R&D. That is only a single printhead over here. Now again, the key highlight is that this technology does not have any heat, not any UV. That provides us the opportunity to incorporate the widest variety of active ingredient. Again, the printer is enclosed environment and all the weather service area. These are stainless steel 306L, which are very, very standardized pharmacy equipment surfaces. Of course, all these will allow us to produce consistent batches of the tablets ranging between plus minus one to 3% for the weight uniformity itself.

Speaker 3: 42:59

This is really just a simple video of how we can actually paint two different tablets with two different ingredients at the same time, thereby cutting down our production rate Sorry, cutting down the production time involved. So, as a rough gauge, 100 mg two materials tablet and I can relate to get about 10 seconds to print one single tablet. Over here we can really do a high degree of customization across different dosage forms, such as the tablets itself, multi-layer tablets. Over here we can also do printing into capsules itself, so a single capsule can also retain different release profiles within the same capsule and some of the dosage forms, like multi-layer. True Oboe itself is also really, really popular, especially in our region over in Southeast Asia, singapore, or even in the Australia APEC region itself.

Speaker 3: 43:53

So really, what we believe is through the use of 3D printing platform for craft health technology itself, we can actually help to mitigate some of these key barriers to mass adoption of 3D printing. So, in terms of technical-wise, our semi-solid extrusion is by far, we believe, to be the one that is suitable for the widest range or the widest variety of active ingredients that could be used through our 3D printing technology and with the use of craft lamps, our standardized premixers and some of the preset printing instructions. On the preset templates itself, we can really reduce the learning curve that is required for any of the pharmacists or any of other clients itself in terms of adopting the 3D printing platform. In terms of logistics-wise, I think we provide a one-stop supply for all ingredients that is required, which is basically our craft blends, and all this supply of quality ingredients is really powered by Brandtech, which is a global distribution company. It is one of our key partners in actually our expansion for all this supply of materials and the premixes, and that's a regulatory-wise. Currently, there's still no guidance, clear guidance, on setting up a 3D printing pharmaceutical facility itself, and we are very, very well aware of that, which is why we have serious work in discussion with our Singapore Standards Council for developing standards on 3D printing in pharmaceutical compounding.

Speaker 3: 45:17

Now, before I head off the discussion over here, I'd just like to share some of the use cases that we have done with hospitals locally in Singapore. So one of them is reducing polypharmacy for the continuous phase treatment of tuberculosis. Tuberculosis is important. It is a community risk if not well-controlled. So in Singapore and I believe probably similar treatment overseas as well there is a direct observation therapy where they require the nurses or the doctors to observe the patient actually consuming the tablets itself. So really what you can do now is to combine the different active ingredients into a single tablet itself, thereby reducing admin burden on healthcare institution, improves adherence to treatment therapy and overall reduction in community risk to the spread of tuberculosis.

Speaker 3: 46:04

The second use case itself is for supplements bariatric supplements, itself with reduced pill burden, that we actually do with another hospital in Singapore, similarly, traditionally I think, post-bariatric surgery. Some of the patients take up to seven different pills itself on a daily basis to prevent their malnourishment of this kind of minerals or supplements in the body itself. And I think a lot of them do complain that it is very cumbersome and often after taking all seven of them they don't even feel like eating their lunch, their breakfast, anymore. So what we do here is to customize the supplements that is required based on the doctor's prescription, and then change that into a tasty, flavorful form that can be chilled itself. So what we provide to the patients with really multivitamin and calcium citric gummies itself that can actually help them to improve compliance and have a better overall taste profile in terms of the supplements that they have to take, so customized dosing and ingredients that are not available commercially. That's something that we can do. It helps to improve adherence and overall improvement in therapy success and health outcomes.

Speaker 3: 47:17

I think this is the last slide. So we have partners around the world and especially, a lot of them are within our region and APEC region itself ranges from distributors compounding pharmacies, and not forgetting a lot of the education institution distributors compounding pharmacies, and not forgetting a lot of the education institutions, distributors, really, and, of course, hospitals, who are one of our major partners as well, and really we are very, very interested for more partnership and we really want to see how all these collaborations, whether be it our region or internationally, can help us to actually push the frontier of 3D printing for pharmaceutical drug delivery in terms of personalized medicine. All right, then. Thank you very much. Happy to answer any questions.

Speaker 1: 48:00

Thank you so much for a great presentation. By the way, all those speakers, feel free to put your contact info in the chat box if you want people to contact you directly, because sometimes it's hard to write down the email addresses. Yes, we have quite a few questions in the audience for you, Se-Han, and so first question is okay, you mentioned G-code and that immediately put some people's guards up. I would say what software can a pharmacist use if they want to print? How easy is the actual process?

Speaker 3: 48:32

Right.

Speaker 3: 48:33

So really, in this case, right, I should not have used the G-code itself, because really G-code is the official file name for all the printing instructions that the 3D printer has.

Speaker 3: 48:43

So really, a pharmacist, if they were to use a 3D printing platform itself, they do not need to sort of dabble with G-codes, they do not need to do any designing work and so on. With our wireless interface and the standardized templates that we have basically together, once they run through our craft-enabled platform, they can just select the desirable template straight away, print them out. So, as of now, we have standardized templates for tablet size ranging from 15 milligrams all the way up to 1,200 milligrams, which we believe that is probably the largest size that a typical healthy adult will be able to swallow. And of course, we have shapes like a standard cylindrical tablet or even an oblong or caplet shape itself. Definitely, we are also looking to implement all the different shapes that are commonly available. So any such shapes that our customers would like to have, they can let us know and we can upload these standardized templates for them to choose from.

Speaker 1: 49:34

So you do not really need to know how to write G-code. That's the answer, right, exactly, that's right.

Speaker 3: 49:39

Sorry for my technical term just now.

Speaker 1: 49:41

Yeah, it's good to know that that exists, because that's what's powering the machine. Okay, another question from Kadi Samuel If the machines were orders of magnitude more productive, would you see opportunities to centralize production and ship products to customers and pharmacies?

Speaker 3: 50:00

Yes, definitely. So. One of the key advantages for this kind of machinery is really that it's automated. It could be automated together with the use of robotic arms and so on. So I would say there's definitely opportunity for this kind of mass production or customized tablets and so on. What the human or what the typical compounding pharmacist may not be able to do is to do 24-7 lifestyle production. So, with a fully automated solution, I think that's definitely something that is possible in the near future and something that we could explore, especially, for example, for hospitals or for brand owners who are looking to actually produce some of these complex geometry kind of tablets or gummies itself for their own usage.

Speaker 1: 50:45

Got it? Okay, we have this really long question. I'm just trying to. You can read it yourself, senghana as well, in the QA box. I think it's okay. So I understand that you need a kind of drug encapsulation to control drug release, but why do you need to print it? For example, encapsulating a drug in PLGA nanocapsule, mixing it with an injectable polymer. Why do you need a specific architecture? So why is the shape important? Layer by layer? Why not just fill the whole of a capsule?

Speaker 3: 51:18

Right, right, right. So definitely that's a common question itself, right For us. Really, what I feel that there's, the key area that 3D printing can actually shine, is really in those that is customized. So really, if you're looking at just a single ingredient tablet, something that we can do for sure, no problem. But I realize that some of the images that we show are really always about multiple ingredients into a single tablet itself. One of these technical advantages over traditional tablet press itself, for example, I think most of us will have seen bilayer tablets in one way or another. For example, something that's very commonly prescribed locally in Singapore is Anorex, that is, paracetamol and orfenadrine stacked together in bilayer. But really for traditional tablet press, anything more than two layers, they're going to have increasing difficulties producing that. So, really, what shines for 3D printing, especially in our craft health printing platform, is really combining three or more ingredients. Itself. That allows us to do that heavy customization that traditional production is not able to do so.

Speaker 1: 52:23

Right Makes sense.

Speaker 3: 52:25

Okay.

Speaker 1: 52:25

One last question. I want to know whether there are 3D-printed commercialized drugs other than Spiritan, which is FDA-approved right now. Do you have?

Speaker 3: 52:38

any. Correct me if I'm wrong. Basically, there are no other FDA-approved 3D-printed commercialized drugs. There are still under clinical trials, especially those that are coming from China. China is aistec itself.

Speaker 1: 52:54

That's a large production machine. Yes, that's right. That's right, Okay, well, thank you so much. We'll come back to you with panel discussion. Thank you so much for great questions, guys. We're going to introduce our next speaker, who is Dr Nicholas Sentler, who is the co-founder and CTO for Curify Labs. He also has a decade-long of research experience and commercialization experience in the field.

Speaker 4: 53:27

Thank you very much. Can you see my screen? I can't see myself.

Speaker 1: 53:33

Presentation mode not yet.

Speaker 4: 53:35

Oh, yeah, yeah, we're in for presentation mode. There we go, maybe.

Speaker 1: 53:38

Yes.

Speaker 4: 53:40

Great. Thank you so much for inviting me to speak today. Such a great session and experts around the table experts around the table. It's my pleasure to speak about Curify Labs and really how we see the world of changing pharmacy compounding and how we can bring automation, digitalization and 3D printing to personalized medicines.

Speaker 4: 54:07

My background is in pharmacy. I'm a pharmacist, phd in pharmacy. I've worked in academia both in Finland and actually New Zealand as well. Then I have, during my career, worked in the industry as well, for instance, as a Seneca in material science in the UK. Then I became a professor at Åbo Akademi University in Finland and during that time we actually really explored the possibilities of 3D printing and other printing technologies in making personalized medicines. And then I've spent some time in a scale-up company, nanoform, and then, finally, we founded Curify Labs to really change the way pharmacy compounding is done and how we can bring more automation through the non-sterile manufacturing of drugs, and to basically take it all the way back. My mother was a compounding pharmacist she's in the picture here and I think I got the spark of being a pharmacist from her and then also solving the problem of manual compounding. So we were founded in 2021. We have a headquarters in Helsinki, which there is in Germany and the US. We have also actually warehouses in Germany and the US as well, so we can provide all the or our services on both continents. Based on 10 years of academic research, we're currently active on 13 markets. Currently 27 members and expanding in the team and, as I said, our main focus is on compounding pharmacies and hospital pharmacies.

Speaker 4: 55:58

But the technology itself it's applicable to, you know, manufacture GMP type manufacture also in the pharmaceutical industry. So one of the problems in compounding and the access to medicines in pediatrics is, of course, huge, as you know. So 50% of the medicines are not available in doses or formulations approved for children. This is why we also exist. We exist for bringing patients the cures they need. So this is why compounding also exists. When there are no registered drugs, somebody needs to do it and somebody is typically a compounding pharmacist or a hospital pharmacist, and there's a need for personalization on different levels. There are different treatment responses, swallowing difficulties, the doses are not correct, both on the human side, but specifically also on the veterinary side.

Speaker 4: 56:58

If we look at the technology development timeline for Curitiba Labs, the academic research started in 2009 when I became a professor. Research started 2009 when I became a professor, and then we founded the company 2021. We started directly working with pharmacies, so we had paying customers who were really wanting to explore the technology. And veterinary patient dosing started already in 2021 in compounding and there I have to correct Alvaro a little bit sorry about that we started compounding pharmacy printing already in 2021 in vets and then 2023 in on the human side, so a little bit earlier than 2023 on the human side, so a little bit earlier than you guys, but all the kudos to you. You've done a great work in the field. So it's great that we have different players in the field. We did this multi-site study in 30 pharmacies across Europe in 2023, published the results in 2024. And during that study, we really collected information from the field. What is relevant for the compounders out there? How should a system like this look like? And then we launched our first official pharma printer and our first GMP manufactured pharmaceutical inks or excipient bases, as we basically call them in October 23. And yeah, the first printings happened already for patients in 2023.

Speaker 4: 58:38

Just if I look basically look into what has been what my research group was doing during 10 years and what led to Curify Labs. So we did this and that within the field you can see, we started with inkjet printing and then both 2D and 3D inkjet printing, fdm printing, flexography, started integrating quality control tools and exploring them different spectroscopic technologies, colorimetry, so on. Even explored inkjet printing and QR codes, where the ink had drug substances in them and the patient information Cool projects, maybe not so applicable in real life Stencil printing. And then we started going more and more into real work cases hospital systems and hospital partnerships, warfare influence in 2019, and then also focus group studies, interview studies within the staff, to understand what to do in the best possible way. This is just to highlight the validation study that we did across Europe in 2023, with a lot of hospitals across Europe.

Speaker 4: 59:59

So automation in pharmacy compounding comes with many benefits. So we can decrease costs by standardizing the methods and the fast compounding. The validated processes, the traceability and built-in quality control tools increase the compounding quality and, of course, in the end, the better patient outcomes are the key. So with the various dosage forms and flexibility in dosing, we can reach that. As you can see, we have a lot of similarities in the speakers from before, so maybe small differences, but obviously we're speaking about the same thing. So we want to change the way manual compounding is done. We've shown in the study that we can be four times faster with the processes that we have created, and I want to highlight that 3D printing as such, or whether it's called blister filling or extrusion directly into packaging itself, it doesn't solve a problem for the compounding pharmacist. It's a complete workflow. It's a complete process. All the steps have to be in place.

Speaker 4: 1:01:08

The technology of Curify Labs supports multiple dosage forms, as you can see in the picture, and let's jump into how it actually works. So we also like to say it's inspired by 3D printing, because it's not solely 3D printing. It's also liquid dosing, liquid handling and so on. But we do create often 3D printing. It's also liquid dosing, liquid handling and so on, but we do create often 3D structures, so in that sense it also can be considered as a 3D printing technology.

Speaker 4: 1:01:40

So our offering for pharmacies is kind of fourfold. We have the proprietary pharmaceutical excipient bases, a software platform, robotics and 3D printing and integrated quality control, and the end result is the standardized dosage forms from tablets to capsules, and you can even you know dose ointments and or dispersible films and so on. Even if we offer these proprietary pharmaceutical excipient bases our system. We don't force our customers to use them. It's fully possible to use other ingredients in our machine as well or find the right parameters in the system. But we have learned that pharmacies are busy and they should be concentrating on the patients, not tweaking parameters in a printer. So we have wanted to come with a plug and play digital component platform for for pharmacies.

Speaker 4: 1:02:45

And in the core of everything is our formulation library, which is growing, growing day by day. You can see here what type of data there is for our customers. We have the human formulations, for instance, and we build in our laboratory quality dossiers for each formulation. So the pharmacists can rest assured that if they use the batch protocols provided they get the stability data, they get the cleaning validation data, they get the solution profiles and process validations of these. For instance here, spironolactone nine months stability. And this is what we do for every formulation in the library. And if we look at basically the therapeutic areas that we cover at the moment, everything that we do comes from the field. So if there's a request from a customer, we start developing that formulation and get it to the library and everybody who has our system can start using that formulation when it's launched. So this is the basic idea, with no extra cost of using that formulation when it's launched. So this is the the basic idea, with no extra cost of developing that formulation.

Speaker 4: 1:03:55

So the workflow. Workflow is simple. There's an order order creation, weighing, mixing, dosing and then sealing, labeling. And if we look at an order order creation here, let's see if it starts there we go. So, basically, simply, from the formulation library, you choose the drug that you are going to dose Ramipril in this case then you choose the dose you can also choose multiple doses if that's interesting and then reasonable and then the number of tablets and then you create the order. The order is created on a web app which is then sent to the printer that you're using. So you can have multiple devices. You can control all the order handling centrally.

Speaker 4: 1:04:46

Let's look at the excipient bases really quickly. These are GMP manufactured bases, which means that they are produced under the same robustness and quality than any drug product on the market. So all the excipients are pharma grade, analyzed according to GMP and released according to GMP. Analyzed according to GMP and released according to GMP. And currently we have these bases on the market. So gel tablet base, suppository base, two different anhydrous bases, oral films and then these chewable gel tablets for veterinary purposes as well. So why these type of bases? We need to be able to cater, of course, to different types of dosage forms, but then also drug substances have different properties, so then we need to be able to match those properties to the API. Obviously and here you can see some presentations of the tablets from the field, so you can see there are differences how they look like. So once again, the oral bases are GMP manufactured and they are all optimized for this automated dosing system.

Speaker 4: 1:06:05

There are a number of excipient bases out there, but they are obviously not optimized to work in these printers always in the most optimal way. So that's at least a guarantee from our side that if one uses the CuraBlend bases, that's then studied properly and we provide all the for our customers. We provide all the information about the ingredients in there, because the prescribers need to understand what components are there, Are they suitable for pediatric patients and the allergies that patients might have. So we disclose everything that's in there. The beauty of printing. We've heard of the flexibility of dosing. This is just an example of how we can dose very flexibly any dose and of course, the kind of the promise of 3D printing or this type of automation technology is that you can alter the dosing regimens and then, of of course, combine tablets A little bit of the regulation.

Speaker 4: 1:07:16

I would say that it would be great that we also, as a joint force, from the people who are active in this field, of companies. Typically, when we use 3D printing technologies we produce tablets or dosage forms in general that are already described in the pharmacopoeias. So from that point of view there's no regulatory hurdles or regulatory differences. For instance, for a tablet machine, if you read carefully the USP or the European Pharmacopeia, in the introduction here it says that tablets can be produced through extrusion. So by definition it would mean that extruded tablets can come from a 3D printer. So that's kind of my message too, because often there is a little bit too much emphasis that there should be regulatory sort of guidance. Of course there has to be an understanding also, but it doesn't differ so much. The end products are dosage forms that exist. We take quality seriously and that's where we have a certificate ISO certificate on the 13485, which is a medical device certification. The machine itself is not a medical device, but it.

Speaker 1: 1:09:32

Thank you, okay. Okay, I thought that was the problem, but I guess we lost him. I will sure to help revive Nicholas there, but meanwhile, since I don't know when we're gonna to have him back, maybe we should just start with our next speakers also giving time plus. So I'm going to introduce our last but not the least speaker, dr Thomas Forbes. Thank you so much for staying until the end for the finale. So okay, I need to do a proper introduction. Dr Forbes is a research scientist at the National Institute of Standards.

Speaker 4: 1:10:17

Oh, you're back, I'm back, sorry, I wasn't sure, so I have to start the next one.

Speaker 1: 1:10:22

So maybe we can also kind of just wrap up if you're already at the end.

Speaker 4: 1:10:28

Yeah, can I? Yeah, maybe I'll do it. Yeah, go ahead, go ahead.

Speaker 1: 1:10:30

Well, I will reintroduce Dr Forbes.

Speaker 4: 1:10:33

Yeah, sorry about that. I don't know what happened. Yeah, can I use a few more minutes or?

Speaker 1: 1:10:38

Yeah, please, yeah please.

Speaker 4: 1:10:43

Okay, so a standard process would look like this Very simple, weighing the API and the XDP base.

Speaker 1: 1:10:49

Your screen is not shared, just so you know.

Speaker 4: 1:10:52

Oh, that's strange.

Speaker 1: 1:10:55

So we're going to skip the question part, since we're kind of short on time now yeah sure, sure.

Speaker 4: 1:11:04

Can you see it now?

Speaker 1: 1:11:08

You're in a different kind of presentation mode. Okay, yeah, there you go.

Speaker 4: 1:11:15

Okay. Okay, so the process was shown there. You can see the printing happening. Here we have an integrated scale in the system, obviously 100% mass uniformityity. If the printed tablets are out of spec the circle on the screen would be red and then it would prompt you to replace that tablet. But you can see the speed of printing is about one to two, one to three seconds per tablet, depending on, basically, the dosage form. And here just a similar example from Kraft Health iso-niacin rifampicin layer tablet. So basically you just dispense the tablets on top of each other and then form a multi-system tablet and we have customers shown time savings, for instance for suppository manufacture 18 minutes time saving for 30 suppositories compared to manual methods.

Speaker 4: 1:12:14

And then very quickly use cases from hospitals. The technology is in clinical use and these are cases from Germany, minden Hospital. They started with forest and mild and prednisolone. This is from Tartu. A nice desensitization study for aspirin Worked a lot with rare diseases.

Speaker 4: 1:12:37

This is for one compound, epalrestat. This is from Naples. Leukemia patients have been treated with dasatenib and our tablets were really well-received. 20 patients dosed AT preferred our gel tablets. Princess Maxima Center Cancer Hospital in Europe mines doing a large palatability study. At the moment we have a large compounder in Sweden basically doing all the compounding in Sweden using two of our devices and then compounding pharmacies in US. This is one, this is another one and St Jude Children's Hospital are starting implementation as we speak. We just came out with a study on hydrocortisone dosage forms where we did a tech transfer there on those, and we're also active in drug shortage agile manufacturing project. We're running this RoboFarm project in Europe. So it's about basically preparedness and so on. So thank you so much. 3d printing is reality already, as we've heard today, and there's room to grow. There's a lot of basically benefits from the technology and thank you so much for listening.

Speaker 1: 1:13:57

Thank you, niklas, sorry to rush you at the end there. There are a couple questions in the Q&A box you can type in the answer. They're great questions, but we just have to move on.

Speaker 1: 1:14:07

Of course, and also this is to all the speakers If possible, I'd like to request a copy of your presentation to share in PDF files. It's totally fine Later on with the audience in case people miss some details, if they want to go back and take a look. All right, so let's move on to our final speaker, finally, dr Forbes. Thank you so much for joining us today. He is a research scientist at the National Institute of Standards and Technology, an agency of the United States Department of Commerce which advances critical measurement solutions and promotes equitable standards to stimulate innovation and industrial competitiveness, and he leads a program at NIST investigating the measurement science and potential standards needs for a pharmaceutical production paradigm that shifts towards agile distribution and point-of-care manufacturing. Take it away, tom.

Speaker 5: 1:15:06

Great. Thank you for the introduction and thank you for everybody sticking around. And so I'm Tom Forbes and I'm going to talk more about the metrology here and try and kind of focus on the things that might be different from the other presentations and kind of give a different perspective, not being commercial. So just real quick disclaimers and disclosures any of the opinions are my own and not the policies of NIST or the US government. Any commercial products I mentioned are not intended to be a recommendation or endorsement by NIST and I have no competing financial interests. And so, real quick, if you're not familiar with NIST, the National Institute of Standards of Technology, we were originally founded in 1901 as the National Bureau of Standards in the US and then later in the 80s became NIST and we're a non-regulatory federal agency in the Commerce Department. And so we are the US's National Measurement or Metrology Institute, an NMI, and countries around the world have these NMI's for setting measurement standards in related areas. And so the NIST mission is to promote US innovation and industrial competitiveness, specifically by advancing measurement science, standards and technology. And so that's where I'm going to try and focus today. And so NIST does a wide range of things. We do things from disaster failure studies, so investigating the collapse of the World Trade Centers. Reference materials you might be familiar with physical materials reference data calibration services. Nist plays a big role in documentary standards and these are usually in collaboration with ASTM or ISO. And then we also investigate critical and emergent technologies and we have a large intramural and extramural manufacturing program, and so for all these things we're really looking to aid for the adoption of technologies, those that are critical today and then things that are coming up in the future, and we do anything from basic to applied research, and a lot of this has to do with manufacturing and standards, and so all those things kind of have combined with this increase in point-of-care medicine, 3d printing, those technologies, and a lot of this was summed up nicely in a paper by the National Academies of Science, engineering and Medicine that was really focused on advanced manufacturing technologies for pharmaceuticals, and so this ranged from high-throughput things like continuous manufacturing to 3D printing and additive manufacturing, which we've seen in the last three talks, and the overall idea being to improve quality, address things like shortages and, for new drugs, improve that time to market. And so with a lot of these technologies, specifically the 3D printing, additive manufacturing, everything we've seen today we can move more from having a single centralized manufacturing that's doing high throughput, a select number of doses, to something that's more distributed, where there are smaller, either distributed manufacturing sites or even point of care manufacturing. And so this is a lot of what we heard Can you put these printers into pharmacies, into hospitals, right where the patients might need them? And this is a schematic kind of how this might look in the US or around the world.

Speaker 5: 1:18:15

On the right here of why you might want to be able to personalize your medicine. Some of it is the agile response to localized needs. If there is a natural disaster or an epidemic that's localized, can you increase production in that local area. Personalization for specific patient groups like pediatrics or geriatrics, allergies that you might want to remove a component from doses. Rural pharmacies in the US make up almost 90% of the pharmacies, yet they might not have access to every single dose level or immediate supplies of those, and can they produce those on site. And then we're getting into small batch clinical trials, hospitals, urgent care, and we've heard a lot of this and great examples of how this is actually being done currently, and so in the past few years FDA has also had, so the Food Drug Administration in the US has had a workshop and reports on this distributed manufacturing idea and how they can prioritize this distributed and appointed care manufacturing. And then, of course, being they are a regulatory agency, how can they make that framework about science and risk-based? And so this is kind of where NIST can play a role into helping to develop the measurement science, what control strategies on certain analysis, a lot of what we do for a lot of areas towards this 3D printing of pharmaceuticals, and so this would be to support production, equipment, technology and industry. Like we've seen from the speakers today, it could also be process analytical technology, so companies making those quality control, quality assurance instrumentation that might work in conjunction with them, and then helping other agencies, government agencies or regulatory agencies understand how this works and in what areas are limitations and whatnot. And so we've kind of heard exactly how this might work through the last couple of talks.

Speaker 5: 1:20:09

But there can be a scenario where you still have a centralized or distributed manufacturing site producing a pharmaceutical ink that is then distributed to your pharmacy and that is already formulated, and then you're producing these personalized dosages or specific needs on site, and so we've kind of looked at this, the metrology around this, based on three kind of separate units here that active pharmaceutical ingredient, the ink, the formulation on the front end, then how you're depositing it. So this has been 3D printing extrusion. I'm going to discuss a drop-on-demand printing technique and then what your personalized dosage might be. In this case the delivery vehicle could be tablets, but it could be a number of other things, and so we've heard about a lot of active pharmaceutical ingredients that have been demonstrated today.

Speaker 5: 1:20:57

We've been interested so far in narrow therapeutic index drugs, so things that you have to have precision over and you might be adjusting for your patient across time. So you might want to increase a little bit, but anything too much as it could be toxic, too little is not effective. We've also looked at SSRIs, so antidepressants and also opioids, so things that you might want to taper off of or your doctor might want to adjust on the fly. So can you do small batches of these and have it personalized. And then we have other government agencies that are very interested in medical countermeasures, so there's a list of medical countermeasure drugs and can we have the ramp up of this kind of production localized, based on natural disasters, supply shortages, that type of thing, and so this is kind of where we've been looking.

Speaker 5: 1:21:45

That second component is going to be your deposition, your 3D printing, your solid state extrusion. In this example, basically, we were using a semi-solid extrusion, like you saw in a couple of the videos so far, to print blank tablets, and so the tablets will just have your excipients and your bulk material, and then we use a drop on demand system that can put down precise amounts of your API, your API ink, into those semi-solid tablets, as they're still liquid and solidifying, and so, just kind of a schematic here you have the nozzle with a pressure pulse and then there's an LED and photodiode to count each one of those droplets, to kind of give you that real-time feedback of your dose control by tablet. And so then, finally, the delivered vehicle, and I think we've seen examples of this across the board today. This could be anything from tablets, oral dispersible films, capsules, single-dose liquids you know I've seen a lot of these for pediatric drugs but, as we've heard from the questions, questions too the API or your dissolution profile or the patient themselves might actually dictate what is the most appropriate vehicle for your use, and so one of the big things that the FDA in the US is interested in is usinga quality by design approach for this pharmaceutical development, and so really they're trying to have the quality and the assurance I guess is a kind of design into the beginning of the process. And so they want you to understand the product of processes when you're designing your whole throughput. And so this also involves a risk assessment. So what processes have the highest risk, what increased variability, what might lead to negative outcomes in your production, and then what control strategies do you have in place for these? And so all of that is going into the final goal of ensuring safe and effective clinical outcomes for the patients. And as I talk about a couple of these, I was happy to see that this was addressed in pretty much all the presentations today of how these companies are putting in control strategies and traceability.

Speaker 5: 1:23:53

And so in this quality by design, you can often think of each process as a pharmaceutical unit. You can think of what's coming in and you want to evaluate the critical material attributes of what's coming into this process. You want to understand what process parameters are playing a role and then identify the critical ones, and then what is coming out, what output materials, and then what are the critical quality attributes for that. And this is just an example of how you might look at, you know the material properties for the bulk, the API, other excipients, how you're affecting it. So with 3D printing it could be the pressure, the temperature, these types of things. And then quality attributes can be the quantity, content, uniformity a lot of what you traditionally have seen with pharmaceuticals and this can also kind of be done in series method, where the output materials or the quality, critical quality attributes of your first process can then be the input materials for your second process and then again those outputs become the inputs for the final one, until you have your final product.

Speaker 5: 1:24:55

And just to give a couple examples, we can look at the API deposition and we can investigate parameters that are critical to that drop on demand dosing, and we can look at where the biggest, highest uncertainty comes into play, based on the number of droplets, the liquid properties, the printing properties, and then we can have the credit quality attributes coming out. So do we know the exact dose of what we've put down in each of these? And then we can move to the next stage, which would be the delivery vehicle, and this is looking at an example of cytoprame tablets, and this is looking at an example of cytopram tablets, and so this first figure is your blank tablet. So this is semi-extruded into a tablet mold, or it could be a blister pack or capsules, as we've seen. And then the drop-on-demand system is putting the two milligrams of cytopram into each one of those tablets, and so our critical quality attributes for that final product are going to be is this the dose we meant to print? And then do we have a content uniformity? Are we pruning all the doses the same? And so a big way to address the control strategy. So where is the highest amount of risk? And then where can we put in steps and verifications along the way?

Speaker 5: 1:26:05

And so we kind of just went along our three unit operations here and we can look at at-line verification of that ink that you're starting with in-line monitoring of your production and then at-line or online confirmation of what you've produced, and so this can look like you're taking your ink, you're using a spectroscopic technique. So this is an example just using simple UV absorption where it's a Warfarin pharmaceutical ink and you can see that after a week you know you're still in the liquid phase and then after a couple months that Warfarin will start to crash out a solution and you can see this difference in your absorption and you can catch that ahead of time. And so this could also be if you know it was sitting on the tarmac and there was some degradation, can you catch it before you even start your printing? For the system we were looking at, you can get a traceable report for each dose for the number of droplets. So if you miss droplets you have the choice to go back and redeposit those into that specific dose. You can eliminate that dose from your batch.

Speaker 5: 1:27:06

But you're having this real-time measurements and we've seen with the talks you can have real-time measurements of the gravimetry of the tablets as they're being produced microscopy and I'll mention that a second here when we get to the atline and online batch confirmation, and so there are a lot of analytical techniques. You can gravimetry for measuring tablet weights. You can actually measure tablet droplets being ejected. Microscopy is big in your traditional 3D printing, so can you use machine learning or AI to identify when a print is going bad prior to finishing Spectroscopic techniques.

Speaker 5: 1:27:40

We've heard about NIR, ir, uvviz, raman and a lot of the metrology we're doing is helping regulatory stakeholders and industry understand limitations of some of these measurements and you know, for example, raman, if you're getting into a low concentration, into a high bulk material, you're going to have difficulty seeing that low concentration API. And so what are the limitations of these instrumentations that someone might want to put in place for this area? And then, as the printing technologies improve and increase, we've also seen an improvement and decrease in size for more on-site, very specific technologies such as mass spectrometry. And so as these instruments become smaller and smaller, they may not be something you're seeing at a pharmacy, but if you have a distributed manufacturing site or one of these on-demand pharmacies where you're rolling up with a number of trailers and you're setting up a pharmacy in a natural disaster, you might have this analytical technology for your quality control. And so I was happy to see this with these companies too A traceable production report.

Speaker 5: 1:28:48

You know this is critical for understanding what you started with. What's in the doses? What the batch looks like, is the content uniform? Are the doses correct, that type of thing. We saw that again and again today, and so most of what I've talked about has been measurement science. But I also want to, you know, socialize with the community and everybody here today kind of more. What can we do beyond the measurement science. So standards, documentary standards, what could really push adoption of these technologies and help not only pharmacies, hospitals, implement this, but what might regulatory stakeholders want to see or need to see? And so standards are critical kind of for enabling comparison and interoperability across these different technologies. And as more come out and emerge, we want to promote the research manufacturing innovation.

Speaker 5: 1:29:41

Can some of these technologies and these unique capabilities been translated across technologies, expanding adoption? Obviously in manufacturing capacity? If this is going to play a big role, how can we increase that capacity for this type of technique? Secure supply chain, cyber, as we see, a lot of these have very sophisticated softwares with them. Can we ensure that those are secure within themselves? And then, if they're speaking to each other across that type of a supply chain and then streamlining the regulatory review Again, can we help the regulatory agencies understand what they need and what might be the limitations and the benefits of this type of thing to reduce the cost and time to market?

Speaker 5: 1:30:26

And so this is kind of really for us at NIST interacting with the stakeholder community. You know everybody here pharmaceutical industries, public health organizations, the hospitals and pharmacies themselves, instrumentation industry. So that's everybody who's spoken today. That's also the process analytical technology industry. And then patients, you know, and then patients, you know, we need patients to be confident in 3D printed drugs. We need them to be assured that what they're taking is as good as what they might get from a high throughput centralized manufacturing site.

Speaker 5: 1:31:00

And so, really, nist is interested in identifying are there new measurement science areas that need to be addressed? Standards Obviously, us Pharmacopoeia has a lot of monographs and specifics for compounding in the traditional sense. Can we help evolve those and, you know, work with them on specifics for something like this, and, again, engaging stakeholders. So this could be NISLEDGE Consortia, this could be some of the other international organizations that bring in US Pharmacopoeia, regulatory agencies, partnerships and other workshops in this type of area. And so then I'm just going to wrap up with one last slide and just kind of give you an idea of potential avenues. And so these are areas that have come out of NIST that are similar but might be applicable to something like 3d printed pharmaceuticals. And so um nista collaborated on a standard guide for bio inks using bioprinting, and so this was put out through astm, and so it's really kind of developing and providing a consensus terminology for how you're talking about these things material properties that are critical for bio inks in bioprinting, different printing modalities, and so these types of documentary standards can be used for somebody to point to, for you know where to get started, how to do things, and this could be ASTM, it could be ISO, it could be NIST guidelines, it could be US Pharmacopoeia, but those types of things might help everybody kind of be working from the same playbook.

Speaker 5: 1:32:25

Nist also has reference data and tools. So this could be standard reference data, which is often provided through vendors, or it could be more just public data repositories. So NIST publishes all data from studies, but also does libraries and databases. So there's a NIST NearIR sort database and this is NearIR Spectra for textiles and it's meant to aid in the textile recycling industry and they're specific to have you know the database of the Spectra. They've made it all machine learnable. There's a lot of machine learning AI going into NearIR for recycling, and so is something like that useful for this community. Another example is the NIST Dart MS Forensics Database, and so is something like that useful for this community. Another example is the NIST Dart MS forensics database. So this is mass spectral database specific to forensics. You know has over a thousand compounds. But it not only has the library, it also provides a free and openware data interpretation tool. So how you can match the library with your spectra.

Speaker 5: 1:33:24

Inter-laboratory studies are a big thing that NIST likes to produce or participate in, and so NIST has a larger additive manufacturing program and they've put out interlaboratory studies with ceramic additive manufacturing, where they looked at a number of laboratories using the same printers, and also polymer, photopolymer additive manufacturing, whereas 24 laboratories using all different types of printers, and they're trying to look at the interoperability of working curves developed for those VAT photopolymerization things.

Speaker 5: 1:33:56

And then finally, reference materials. You know US Pharmacopoeia has a lot of reference materials for traditional pharmaceutical areas. Nist has a monoclonal antibody reference material and then other reference materials that are more not the drug themselves but related to those types of productions, and so is something like this maybe, you know, maybe a test grade material or test grade formulation for everyone to kind of be used to verify or calibrate systems, and so hopefully this kind of gives you a flavor of what might be useful and what might help the industry, but kind of giving a different perspective. That's the presentation today and thank you for listening and thank you to all the other speakers today. It was great to participate.

Speaker 1: 1:34:42

Thank you so much. Wow, this is like a whole new field that I never knew. I didn't know about NIST and now I realize how important you guys are. Okay, one question from the audience, from Luciano Bragio. Very insightful presentation, thank you. Are you in the process of conceiving any ad hoc process analytical technology workflow for these type of manufacturing technologies? Have you heard of this?

Speaker 5: 1:35:10

So a lot of what we're doing is kind of investigating the measurement science limitations and where areas work for process analytical technology. We are not necessarily developing new novel process analytical technology. This does develop technology. I don't know that we are looking at that in this area, but it's more of these are the technologies that are being used and we know like we heard a lot about near IR and obviously Raman and UVViz and other spectroscopic techniques are being used, and so we're usually investigating those for this specific area. How might they be implemented? What limitations might they have? Kind of to give the community something to work off of.

Speaker 1: 1:35:49

So already pre-existing technologies, anything that actually is, I mean might as well just bring all the panelists to the screen. Now to ask this question is for the quality control process, the whole thing that we've been listening in the last 15 minutes. Is there anything that's 3D printing only that other traditional manufacturing process does not rely on? But because we have a new process and therefore we need a new quality control process. I mean for like yeah, yeah, you can start.

Speaker 5: 1:36:24

A lot of it is, or at least for the analytical technology where you're looking at. You know a signature or something. It's for dose measurement, and so you're trying to quantify that what you have is correct and that's going to be the same across traditional pharmaceuticals and these. You might have different excipients in your 3D printed things, but the technology is going to operate the same either way.

Speaker 1: 1:36:48

Okay, that's actually reassuring. All right, so we are definitely over time, but I like to just have a little bit of a panel discussion, if people are okay with that. So I like to bring everybody on screen, okay. Well, number one question is very general. So what is your number one challenge right now along your line of work?

Speaker 5: 1:37:09

I'll start with you, thomas, since you're the last speaker are there critical needs that still don't exist, and how the 3d printing needs are unique to this area, um, that aren't already being addressed by you know, the pharmacopias or the other uh, you know astm, iso, and so there are some unique areas, and so kind of our challenge is understanding where nist might play a role and help out, and then what I think what FDA really wants to see, or how they're going to. You know, is this just going to be traditional compounding? And then the technique. The technology doesn't actually matter, it's more about the drug. Will it stay that way?

Speaker 1: 1:38:01

Okay, well, I think we have a couple of experts that can maybe answer that question or help on that, so I'll start with Alvaro. What do you think?

Speaker 2: 1:38:11

Well, I don't have a clear answer because it depends from country to country as well, so we are not talking about legal requirements. For example, here in the UK right now I'm in London there is a new regulation that is, point of care and modular manufacturing, where there is going to be a control site that is going to control different manufacturing sites, but the manufacturing sites are not going to be inspected by regulatory authorities. So this is new. I think many countries are going to get something similar. I think many countries are going to get something similar. We are involved in the quality innovation group from the European agency and they are thinking about doing something similar.

Speaker 2: 1:38:59

We have discussions with the FDA in the emerging technology program and I remember in 2022, the FDA organized a webinar about this distributed manufacturing. I think in Europe it's called decentralized manufacturing, in the US it's distributed manufacturing. So the regulation is going to change. We don't need a change in the regulation if we go through compounding. So that's why we are using 3D printing in hospitals and pharmacies and it's totally legal. But if we want to move into something better that adds additional layers of quality for the patients, I think what Thomas is doing, and the USP as well, because we have conversations with the USP for new monographs. Potentially is going to be very important, because for us the aim is not just to implement the technologies to prove that it's safer, faster, cheaper, better, better, definitely.

Speaker 1: 1:39:59

Anyone else has input on that? Oh, if I can, just yeah, sorry, let's go here.

Speaker 4: 1:40:06

Okay, yeah, yeah, I mean mean I agree with alvaro there. Uh, for the compounding part, you know it's it's pretty clear. Of course you know it doesn't take away the regulatory discussions in each region. They are, you know the regulators approach them a little bit different. They want, they want to understand, but the compounding sort of space is pretty defined. Whether it's a border pharmacy in the US, in a specific state, that you know takes a standpoint. You typically, when they see something, they understand that you know this elevates the quality of compounding, you know, to a better level as it is, you know. So that's one part and same goes with Europe. Then, yeah, of course you know, with the industrial sort of part, and then the point of care, personalized medicine manufacturer, where you start having sort of flexible dosing, maybe authorized drugs with flexible dosing it's going to. You know that needs guidance and thinking and we need to work together on that part.

Speaker 1: 1:41:16

Okay. Well, what's your number one challenge at the moment at BigLoss?

Speaker 4: 1:41:24

Well, if we take a practical challenge for the company, I think we are in a phase where we are. You know there's growing interest. It's more like a scale up issue that you know we can grow in a meaningful way and then, of course, get on board the other people that are not the innovators. So I think we still need to work with establishing the use cases. And then there's growth. Then we unfortunately struggle with the. Obviously we would like to have all these spectroscopic tools implemented with all the, all the drugs and you know. But it's of course a nightmare to if we have a hundred formulations in the, in the, in the library and and to have that multivariate model for everything. It's obviously almost impossible to do. So we can't. You know we can't tackle that easily.

Speaker 1: 1:42:30

So money or people? Which one, which one do you need most at the moment?

Speaker 4: 1:42:37

Probably time Time If you would want to do that, well, of course, money and people would do that.

Speaker 1: 1:42:46

Good answer, Sehen. What about you? What's your number one challenge right now?

Speaker 3: 1:42:50

Yeah, really I think it's really similar to what Nicholas mentioned, right? So number one challenge is really how do we convert those who are really interested? They heard about 3D printing. How do we convert them to be a user of this 3D printing technology? They all have their own concerns. Some concerns are in terms of money how much investment do they have to make? Some concerns about how is it going to make money after that, how are they going to learn to use the machine, so and so forth. So a lot of things that we do is really to try to reduce those barriers and we are seeing some increasing update, but really I think the work for us to do is still a lot ahead. So hopefully, with all this webinar series that you have hosted, we can get more conversion of these people who are interested into the end users of our technology.

Speaker 1: 1:43:40

Yeah, I think it's not just innovation within 3D printing itself, but also innovation in economics how to be creative in business and I've seen so many creativity today. So thank you so much for sharing how you are participating in this revolution, and I do think that the space is growing simultaneously with many other industries, like compound medicine itself is actually a growing industry itself, so hopefully the market is growing. I don't think it's a zero sum game, even though I know some of you guys may be competing for the same market, but I think the pie is big. It's big enough for everybody, and now it's just time to penetrate the market. That is the challenge.

Speaker 1: 1:44:23

So thank you so much for spending time with us today Great. I'm sorry we can't address every single question, but you can always reach out to our speaker. I have linked them on our website in terms of, you know, communication. Their linkedin profile is linked, so if you want to message them, feel free to do so. This is on demand after the end of this, so feel free to share the link. It's going to be on our Zoom account for a couple of weeks, so thank you so much everybody for joining us and hope to see you soon again.

Speaker 2: 1:44:56

Thank you. Thank you very much.

Speaker 3: 1:44:57

See you around.